Purpose: The objective of this study was to identify distinct groups of fatigue trajectories among women with breast cancer and to evaluate whether age, anxiety symptoms, physical activity, and type of treatment were associated with belonging to the most adverse fatigue group. Methods: Women scheduled for breast cancer surgery at Copenhagen University Hospital, Denmark, were consecutively invited to participate in the study (n = 424), resulting in 290 women included in the analyses. Semiparametric group-based mixture modeling was used to identify distinct trajectories of fatigue assessed the week before surgery and 4 and 8 months later. Logistic regression analysis was used to evaluate differences in the distinct fatigue groups. Results: Two distinct groups of fatigue trajectories were identified. One group (21 %) had a high mean level, while the second group (79 %) had a low mean level of fatigue throughout the study. In multivariate analyses, sedentary physical activity (OR 5.78; 95 % CI 1.41–23.75), low physical activity (OR 3.17; 95 % CI 1.15–8.74), and increasing anxiety symptoms (OR 1.23; 95 % CI 1.14–1.33) before surgery were significantly associated with being in the high-fatigue group. Conclusions: The results show that one-fifth of women with breast cancer experience continuously high fatigue up to 8 months after surgery and may have been more anxious and physically inactive. This knowledge is important in targeting interventions to women with fatigue throughout their treatment and who do not return to a low fatigue level with existing treatment, self-management, or support.